The current epidemic of opioid addiction and the high rates of overdose demand novel approaches to understanding what brain mechanisms underlie the choice between drug and non-drug rewards. To establish a clinically relevant basis for investigating this cognitive dimension of addiction, we are establishing animal models of reward choice that are amenable to multimodal imaging approaches for investigating brain systems implicated in decisions to use drugs, in particular opioids, over non-harmful rewards. A key aim in this work is to establish models that generate data in the same non-invasive imaging modalities as human investigations, and then base invasive preclinical studies on areas of concordance with the clinical data. Ensuing studies will have greater potential for establishing specific cellular/systems level mechanisms underlying addiction, and by consequence, potential targets for treatment.